The mutational landscape of MYCN , Lin28b and ALKF1174L driven murine neuroblastoma mimics human disease

Oncotarget
Bram De WildeFrank Speleman

Abstract

Genetically engineered mouse models have proven to be essential tools for unraveling fundamental aspects of cancer biology and for testing novel therapeutic strategies. To optimally serve these goals, it is essential that the mouse model faithfully recapitulates the human disease. Recently, novel mouse models for neuroblastoma have been developed. Here, we report on the further genomic characterization through exome sequencing and DNA copy number analysis of four of the currently available murine neuroblastoma model systems (ALK, Th-MYCN, Dbh-MYCN and Lin28b). The murine tumors revealed a low number of genomic alterations - in keeping with human neuroblastoma - and a positive correlation of the number of genetic lesions with the time to onset of tumor formation was observed. Gene copy number alterations are the hallmark of both murine and human disease and frequently affect syntenic genomic regions. Despite low mutational load, the genes mutated in murine disease were found to be enriched for genes mutated in human disease. Taken together, our study further supports the validity of the tested mouse models for mechanistic and preclinical studies of human neuroblastoma.

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Citations

Jan 29, 2020·Cancer Metastasis Reviews·Alvin KamiliJamie I Fletcher
Sep 29, 2019·Pharmacological Reviews·Peter J Houghton, Raushan T Kurmasheva
Nov 27, 2021·Current Protocols·Andrew J GiffordMichelle Haber

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Methods Mentioned

BETA
transgenic
exome sequencing
PCR
DNA assay
exome capture
Feature Extraction
electrophoresis

Software Mentioned

fastx
bowtie
PyMol Molecular Graphics System
seqplorer
Genome Analysis Toolkit ( GATK ) unified genotyper
Feature Extraction
ViVar
SeqPilot
4Peaks
samtools

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Cancer Genomics (Keystone)

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